Pyridine → HCID 67442569, compound

HRID 1400848Notes

Reaction equation

HRID 1400848 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]2[CH:16]=[C:17]([C:19]3[CH:20]=[N:21][N:22]([CH2:24][CH2:25][N:26]4[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]4)[CH:23]=3)[S:18][C:11]=12)[NH2:5].[N:33]1[CH:38]=[CH:37][CH:36]=C[CH:34]=1.ClC(OC1C=CC=CC=1)=[O:41].C1(N)CC1>CN(C=O)C>[CH:38]1([NH:33][C:34]([NH:5][C:4]2[CH:6]=[CH:7][C:8]([O:9][C:10]3[CH:15]=[CH:14][N:13]=[C:12]4[CH:16]=[C:17]([C:19]5[CH:20]=[N:21][N:22]([CH2:24][CH2:25][N:26]6[CH2:27][CH2:28][N:29]([CH3:32])[CH2:30][CH2:31]6)[CH:23]=5)[S:18][C:11]=34)=[C:2]([F:1])[CH:3]=2)=[O:41])[CH2:36][CH2:37]1

Participants

6

Reactant 4

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 69828CyclopropylamineHCID 58474361HCID 58474361, compound

Product 1

HCID 67442569HCID 67442569, compoundYield 12.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 153 (203 mg, 0.449 mmol) and pyridine (0.109 mL, 1.346 mmol) in DMF (10 mL) at 0° C. under nitrogen was added phenyl chloroformate (1.76 mg, 1.121 mmol) and the reaction mixture was stirred at 0° C. for 2 hrs. Cyclopropylamine (128 mg, 2.243 mmol) was added and the reaction mixture was heated at 55° C. for 5 hrs. The reaction mixture was partitioned between EtOAc and saturated sodium bicarbonate solution, then washed with a saturated ammonium chloride solution and brine, dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography (eluent EtOAc to 30% MeOH in EtOAc) to afford title compound 154 (30 mg, 12% yield). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.43 (s, J=5.48 Hz, 1H), 8.33 (s, 1H), 7.99 (s, 1H), 7.74 (m, 1H), 7.67 (s, 1H), 7.60 (bs, 1H), 7.32 (t, J=8.99 Hz, 1H), 7.22 (m, 1H), 6.63 (d, J=5.48 Hz, 1H), 4.25 (t, J=6.46 Hz, 2H), 2.73 (t, J=6.46 Hz, 2H), 2.55 (m, 1H), 2.45 (m, 4H), 2.28 (m, 4H), 2.12 (s, 3H), 0.61 (m, 2H), 0.40 (m, 4H). MS (m/z)=536.54 (M+H).

Workup

  1. temperaturethe reaction mixture was heated at 55° C. for 5 hrs
  2. customThe reaction mixture was partitioned between EtOAc and saturated sodium bicarbonate solution
  3. washwashed with a saturated ammonium chloride solution and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by column chromatography (eluent EtOAc to 30% MeOH in EtOAc)

Sources & evidence

ORD record
ord-c48eafc1dfc14a3092484e73aed08e7f
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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